Cilia are protrusions on the surface of cells. They are frequently motile and function to propel cells in an aqueous environment or to generate fluid flow. Equally important is the role of immotile cilia in detecting environmental changes or in sensing extracellular signals. The structure of cilia is supported by microtubules, and their formation requires microtubule-dependent motors, kinesins, which are thought to transport both structural and signaling ciliary proteins from the cell body into the distal portion of the ciliary shaft. In multicellular organisms, multiple kinesins are known to drive ciliary transport, and frequently cilia of a single cell type require more than one kinesin for their formation and function. In addition to kinesin-2 family motors, which function in cilia of all species investigated so far, kinesins from other families contribute to the transport of signaling proteins in a tissue-specific manner. It is becoming increasingly obvious that functional relationships between ciliary kinesins are complex, and a good understanding of these relationships is essential to comprehend the basis of biological processes as diverse as olfaction, vision, and embryonic development.
The PCI fold is based on a stack of α-helices topped with a winged-helix domain and is found in a range of proteins that form central parts of large complexes such as the proteasome lid, the COP9 signalosome, elongation factor eIF3, and the TREX-2 complex. Recent structural determinations have given intriguing insight into how these folds function both to facilitate the generation of larger proteinaceous assembles and also to interact functionally with nucleic acids.
The unique innovation of the layered neocortex in mammalian evolution is believed to facilitate adaptive radiation of mammalian species to various ecological environments by furnishing high information processing ability. There are no transitional states from the non-mammalian simple brain to the mammalian multilayered neocortex, and thus it is totally a mystery so far how this brain structure has been acquired during evolution. In our recent study, we found the evidence showing that the evolutionary origin of the neocortical neuron subtypes predates the actual emergence of layer structure. Our comparative developmental analysis of the chick pallium, homologous to the mammalian neocortex, revealed that mammals and avians fundamentally share the neocortical neuron subtypes and their production mechanisms, suggesting that their common ancestor already possessed a similar neuronal repertory. We further demonstrated that the neocortical layer-specific neuron subtypes are arranged as mediolaterally separated domains in the chick, but not as layers in the mammalian neocortex. These animal group-specific neuronal arrangements are accomplished by spatial modulation of the neurogenetic program, suggesting an evolutionary hypothesis that the regulatory changes in the neurogenetic program innovated the mammalian specific layered neocortex.
During mitosis, microtubules (MTs) are massively rearranged into three sets of highly dynamic MTs that are nucleated from the centrosomes to form the mitotic spindle. Tight regulation of spindle positioning in the dividing cell and chromosome alignment at the center of the metaphase spindle are required to ensure perfect chromosome segregation and to position the cytokinetic furrow that will specify the two daughter cells. Spindle positioning requires regulation of MT dynamics, involving depolymerase activities together with cortical and kinetochore-mediated pushing and pulling forces acting on astral MTs and kinetochore fibres. These forces rely on MT motor activities. Cortical pulling forces exerted on astral MTs depend upon dynein/dynactin complexes and are essential in both symmetric and asymmetric cell division. A well-established spindle positioning pathway regulating the cortical targeting of dynein/dynactin involves the conserved LGN (Leu-Gly-Asn repeat-enriched-protein) and NuMA (microtubule binding nuclear mitotic apparatus protein) complex.1 Spindle orientation is also regulated by integrin-mediated cell adhesion2 and actin retraction fibres that respond to mechanical stress and are influenced by the microenvironment of the dividing cell.3 Altering the capture of astral MTs or modulating pulling forces affects spindle position, which can impair cell division, differentiation and embryogenesis.
In this general scheme, the activity of mitotic kinases such as Auroras and Plk1 (Polo-like kinase 1) is crucial.4 Recently, the p21-activated kinases (PAKs) emerged as novel important players in mitotic progression. In our recent article, we demonstrated that PAK4 regulates spindle positioning in symmetric cell division.5 In this commentary, and in light of recent published studies, we discuss how PAK4 could participate in the regulation of mechanisms involved in spindle positioning and orientation.
The THO complex is a nuclear structure whose architecture is conserved among all kingdoms and plays an important role in mRNP biogenesis connecting transcription elongation with mRNA maturation and export. Recent data indicates that the THO complex is necessary for the proper expression of some genes, assurance of genetic stability by preventing transcription-associated recombination. Yeast THO has been described as a heterotetramer (Tho2, Hpr1, Mft1 and Thp2) that performs several functions through the interaction with other proteins like Tex1 or the mRNA export factors Sub2 and Yra1, with which it forms the TRanscription and EXport complex (TREX). In this article we review the cellular role of THO, which we show to be composed of five subunits with Tex1 being also an integral part of the complex. We also show a low-resolution structure of THO and localize some of its components. We discuss the consequences of THO interaction with nucleic acids through the unfolded C-terminal region of Tho2, highlighting the importance of unfolded regions in eukaryotic proteins. Finally, we comment on THO recruitment to active chromatin, a role that is linked to mRNA biogenesis.
IQGAP1 is an important cytoskeletal regulator, known to act at the plasma membrane to bundle and cap actin filaments, and to tether the cortical actin meshwork to microtubules via plus-end binding proteins. Here we describe the novel subcellular localization of IQGAP1 at the cytoplasmic face of the nuclear envelope, where it co-located with F-actin. The IQGAP1 and F-actin staining overlapped that of microtubules at the nuclear envelope, revealing a pattern strikingly similar to that observed at the plasma membrane. In detergent-extracted cells IQGAP1 was retained at cytoskeletal structures at the nuclear envelope. This finding has new implications for involvement of IQGAP1 in cell polarization and migration events and potentially in cell cycle-associated nuclear envelope assembly/disassembly.